Dostarlimab + Cobolimab for Cervical Cancer

Recruiting at 2 trial locations

Overseen By Meghan Shea, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Meghan Shea

Must be taking: Platinum-based chemotherapy

Must not be taking: Immunosuppressants, Herbal products

Disqualifiers: Active CNS metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Up to 2 years

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining two drugs, dostarlimab and cobolimab, to treat cervical cancer that has spread or returned. It evaluates how well these drugs work together in patients who have already tried other cancer treatments. Participants are divided into two groups: one for those who haven’t used similar immunotherapy drugs before and another for those who have. Suitable candidates for this trial include individuals with doctor-confirmed cervical cancer who have undergone previous platinum-based chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use natural herbal products or other 'folk remedies' while participating in this study. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using dostarlimab with cobolimab has promising safety results for treating advanced cervical cancer. In earlier studies, patients generally tolerated this combination well. Common side effects included skin rashes and tiredness, which are usually manageable and not serious.

The FDA has already approved dostarlimab for other uses, providing some confidence in its safety. However, cobolimab is less well-known, so researchers are still carefully studying its safety in trials like this one. Overall, early findings suggest that the treatment is generally well-tolerated, but monitoring for any side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Dostarlimab and Cobolimab for cervical cancer because these treatments work differently from standard options like chemotherapy and radiation. Dostarlimab is a type of immunotherapy known as a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells more effectively. Cobolimab works by enhancing the effects of immunotherapy, potentially boosting the body's ability to fight the cancer. Together, these drugs could offer a powerful new approach to treating cervical cancer by leveraging the body's natural defenses, providing hope for better outcomes.

What evidence suggests that dostarlimab and cobolimab could be effective for cervical cancer?

Research shows that combining dostarlimab and cobolimab may help treat advanced or returning cervical cancer. In this trial, participants will receive both medications. Previous studies found dostarlimab effective for endometrial cancer, with some patients experiencing complete recovery. When used with dostarlimab, cobolimab showed promising results and improved survival rates as an initial treatment for certain cancers. These findings suggest that this combination could also work for cervical cancer. The treatments target how cancer cells hide from the immune system, potentially enabling the body to fight the cancer more effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Meghan Shea, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with measurable, recurrent or metastatic cervical cancer. They must have good organ function and performance status, no severe prior treatment side effects, and not be pregnant or breastfeeding. Those previously treated for hepatitis C can join if cured. Exclusions include past immune checkpoint inhibitor therapy, recent chemo or radiotherapy, active autoimmune diseases, HIV/AIDS, current serious illnesses, use of immunosuppressants or live vaccines recently.

Inclusion Criteria

My cancer can be measured by standard health scans.

Participants must not be pregnant or breastfeeding

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I have never had any type of cancer other than my current diagnosis.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to dostarlimab or cobolimab

I do not use herbal products or folk remedies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dostarlimab and cobolimab daily in 21-day cycles for up to 2 years

Up to 2 years

Day 1 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment with imaging tests every 3 months for 2 years, then every 6 months for an additional 5 years

7 years

Every 3 months for 2 years, then every 6 months for 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cobolimab
• Dostarlimab

Trial Overview The study tests the effectiveness of combining two drugs: Dostarlimab and Cobolimab in treating advanced cervical cancer that has spread (metastatic) or returned after treatment (recurrent). The goal is to see how well these drugs work together against this type of cancer.

How Is the Trial Designed?

Group I: Cohort B: Immunotherapy Exposed Experimental Treatment 2 Interventions

14 Participants will complete study procedures as follows: * Baseline visit. * Imaging tests at baseline visit, at week 9, and then every 12 weeks. * Cycle 1 through End of Treatment (up to 2 years of treatment): • Day of 21 Day cycle: Predetermined dose of Dostarlimab 1x daily. Predetermined dose of Cobolimab 1x daily. * End of Treatment visit with blood tests and imaging tests. * Follow Up Period: Every 3 months for 2 years and then every 6 months for an additional 5 years. Includes imaging tests. If \>= 2 participants with objective responses, then 23 additional participants will be enrolled.

Group II: Cohort A: Immunotherapy Naive Experimental Treatment 2 Interventions

10 Participants will complete study procedures as follows: * Baseline visit. * Imaging tests at baseline visit, at week 9, and then every 12 weeks. * Cycle 1 through End of Treatment (up to 2 years of treatment): • Day 1 of 21 Day cycle: Dostarlimab 1x daily and Cobolimab 1x daily. * End of Treatment visit with blood tests and imaging tests. * Follow Up Period: Every 3 months for 2 years and then every 6 months for an additional 5 years. Includes imaging tests. If \>= 2 participants with objective responses, then 19 additional participants will be enrolled.

Who Is Running the Clinical Trial?

Meghan Shea

Lead Sponsor

Trials

1

Recruited

70+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a phase 3 trial involving 494 patients with advanced or recurrent endometrial cancer, dostarlimab combined with chemotherapy significantly improved progression-free survival, especially in patients with mismatch repair-deficient (dMMR) tumors, showing a 61.4% survival rate at 24 months compared to 15.7% for placebo.

Overall survival at 24 months was also better with dostarlimab (71.3%) compared to placebo (56.0%), indicating its efficacy as a treatment option, although it was associated with a higher incidence of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. Mirza, MR., Chase, DM., Slomovitz, BM., et al.[2023]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab is approved for treating advanced endometrial cancer in patients with mismatch repair deficiency, highlighting its targeted approach to a specific genetic abnormality.

Aducanumab is indicated for Alzheimer's disease and received accelerated approval based on its ability to reduce amyloid beta plaques, although its clinical efficacy remains a topic of debate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Update: Dostarlimab, Loncastuximab Tesirine, and Aducanumab. Gettman, L.[2022]

In a phase II trial involving 155 women with recurrent or metastatic cervical cancer, the combination of balstilimab and zalifrelimab showed a confirmed objective response rate (ORR) of 25.6%, indicating promising efficacy in this patient population.

The treatment demonstrated favorable tolerability, with the most common immune-mediated adverse events being hypothyroidism (14.2%) and hyperthyroidism (7.1%), suggesting that the combination therapy is manageable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study. O'Malley, DM., Neffa, M., Monk, BJ., et al.[2023]

Dostarlimab, an investigational anti-PD-1 monoclonal antibody, shows promising clinical activity, especially in treating endometrial cancer, indicating its potential as a new treatment option.

This antibody is being explored both alone and in combination with other therapies for various cancers, including gynecological tumors, lung cancer, and melanoma, highlighting its broad applicability in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. Rubio-Pérez, J., Hernández, R., Hernández, T., et al.[2021]

Dostarlimab, an anti-PD-1 monoclonal antibody, has been shown to be equipotent to pembrolizumab in suppressing PD-1 activity, with an estimated effective concentration of 1.95 μg/ml based on data from the GARNET trial.

The recommended dosing regimen for dostarlimab is 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks, which supports its use as a potent treatment option for patients with recurrent or advanced mismatch repair-deficient solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. Austin, D., Melhem, M., Gandhi, Y., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06238635

Dostarlimab and Cobolimab in Advanced Cervical Cancer This research is being done to determine how effective dostarlimab in combination with cobolimab is in metastatic or recurrent cervical cancer. Detailed ...

2. withpower.com withpower.com/trial/phase-2-carcinoma-6-2024-15b37

Dostarlimab + Cobolimab for Cervical Cancer Dostarlimab has shown promising results in treating endometrial cancer and has been approved for use in certain cases, with a 100% remission rate reported in a ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1359644623000934

Promise of dostarlimab in cancer therapy: Advancements ... Recent clinical trials have shown that dostarlimab is effective in treating mismatch repair deficiency (dMMR) in endometrial cancer patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10026921/

Dostarlimab: From preclinical investigation to drug approval ... Dostarlimab is a novel IgG4 anti-PD-1 antibody which has yielded remarkable results in mismatch-repair deficient endometrial cancer and locally advanced rectal ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4099

Cobolimab and dostarlimab in the first-line treatment of ... Cobolimab plus dostarlimab yielded promising response rates and survival outcomes with acceptable safety as first-line treatment in patients with CP A, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06238635

Dostarlimab and Cobolimab in Advanced Cervical Cancer This is a non-randomized, open-label, two-arm phase 2 trial of dostarlimab and cobolimab for participants with metastatic or recurrent cervical cancer who ...

7. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(25)00339-7/fulltext

Dostarlimab in combination with cobolimab in advanced ... Based on the encouraging safety and efficacy data, we hypothesize that dostarlimab, combined with cobolimab, a TIM-3 inhibitor, will result in an antitumor ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761174s000lbl.pdf

JEMPERLI (dostarlimab - accessdata.fda.gov Among the 444 patients, 38% were exposed for >6 months and 12% were exposed for >1 year. Mismatch Repair Deficient (dMMR) Endometrial Cancer. The safety of ...

9. gsk.com gsk.com/en-gb/media/press-releases/european-commission-expands-jemperli-dostarlimab-plus-chemotherapy-approval-to-all-adult-patients-with-primary-advanced-or-recurrent-endometrial-cancer/

European Commission expands Jemperli (dostarlimab) ... The most common treatment-emergent adverse reactions (≥ 10%) in patients receiving Jemperli plus chemotherapy were rash, rash maculopapular, ...

10. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-02288

Dostarlimab in Combination with Cobolimab for the ... Giving dostarlimab in combination with cobolimab may kill more tumor cells in patients with metastatic or recurrent cervical cancer. Eligibility Criteria ...